The Microbiome and Probiotics:Fact and Fiction

Ameet Parikh, MD

Human Gut microbiome

- What is it- What role does it play in health and in disease- Modification of the microbiome to maintainhealth or treat disease

Microbiome

Microbiota • The microorganisms that live in an established environment

Microbiome• The full complement of microbes, their genes, and genomes in a particular environment

Microbiome

The Gut Microbiota

- Complex community of microbes – estimated to contain 200 trillion cells

- > 1000 diverse microbial species

- 10 x the number of human cells in our body

- Gut microbiome is 150 x larger than the human genome

Gut Microbiota

Gut Microbiota

Bacteroidetes and Firmicutes make up around 90% ofthe gut microbiota

Each individual harbors his/her own distinctivepattern of gut microbial communities

For a given individual, the fecal microbiota remainsremarkably stable over a person’s lifetime

Prevents colonization by pathogens“Educates the immune system”Metabolic role- Caloric salvage- Produces• SCFA• Vit K and folateParticipates in drug metabolism• Activates 5-ASADeconjugates bile acids

Gut Microbiota - Functions

Gut Microbiota

Colonization of the gastrointestinal tract begins immediately after birth

Initial bacterial colonization (normal) starts from a “Germ free” intrauterine environment and is populated through maternal vaginal/fecal flora and oral feeding (breast milk vs formula)

Complete adult colonization : by 3 yrs of life

Factors affecting Gut Microbiome

Alterations in gut microbiota have been linked with

FBD Metabolic diseasesIBD ObesityCDI MalignancyCeliac disease Type I DMAllergies NASHAutism Depression

Microbiome

Does the intestinal microbiota differ in patientswith specific disorders (IBS/IBD) from healthysubjects?

If the microbiota does differ, is it an importantfactor in the pathogenesis of the disorder?

Gut Microbiota

Gut Microbiota - IBD

Pathogenesis – linked to inappropriate activation of GI immune system toward the gut microbiota in geneticallysusceptible hosts &under the influence of environmentalfactors

Gut Microbiota - IBD

IBS, functional bloating/constipation/diarrhea

Change in gut microbiota – cause abn fermentation ofdietary substrates

elicit excess stimulation of the mucosal immune systemthrough a ‘leaky gut’ – leads to low grade inflammation,affects gut motor responses & elicits visceralhypersensitivity

Decreased Bifidobacterium and Lactobacillus in IBS

Gut Microbiota - FBD

Gut Microbiota - CDI

- Diet- Antibiotics- Prebiotics- Probiotics- Symbiotics- FMT

Gut Microbiota

Global sales of Probiotics – 21.6 billion dollarsin 2010, expected to reach 31.1 billion in 2015

Fastest growing segment of the global dietarysupplement & functional food industries

People are looking for ‘natural’ or non-drugways to maintain health or treat disease

Probiotics

Probiotics

First described by Metchnikoff in 1907

Probiotics

Probiotics Live microorganisms which, when administered in adequate amounts, confer a health benefit on the host

Prebiotics Nondigestible substances that provide a beneficial physiological effect for the host by selectively stimulating the favorable growth or activity of a limited number of indigenous bacteria

Probiotics

Synbiotics

Products that contain both probiotics and prebiotics

Probiotics in the Treatment of Gastrointestinal DisordersDiarrhea

Acute infectiousAntibiotic-associated C. difficile

Lactose Intolerance

FBD

IBDUlcerative colitisCrohn’s diseasePouchitis

H. pylori Eradication

Probiotics

• Able to survive the passage through the digestive system.• Able to attach to the intestinal epithelia and colonize.• Able to maintain good viability.• Able to utilize the nutrients and substrates in a normal diet.• Non pathogenic and non toxic.• Capable of exerting a beneficial effect on the host.• Stability of desired characteristics during processing, storage and transportation.

Characteristics of Effective Probiotics

Probiotics – Diarrheal Diseases

Probiotics - AAD

Antibiotic Associated Diarrhea

Antibiotic Associated Diarrhea

Antibiotic Associated Diarrhea

Probiotics - FBD

10 – 15% of population has IBS

pathogenesis – dysmotility, visc hypersensitivity, disturbances in GI flora, and chronic immune activationleading to low grade mucosal inflammation have all been implicated

Probiotics - CDAD

• First Transplant was in November 2013

• Performed 62 transplants to date for recurrent CDI

• Of the elective cases we have had sustained cures in 57/62 first time FMT- 5 relapses occurred

• 3/5 relapses needed antibiotics after FMT

• 3 competed 2nd FMT, no continued issues to date

• 2 treated with Vanco or Dificid and did not require 2nd FMT

FMT – LGI experience

Probiotics - IBD

FMT - IBD

FMT - IBD

FMT - IBD

Much work remains:

• Is FMT effective and safe in IBD?- Adequately powered trials

• Ideal recipient?- Genotype- Phenotype: Pouchitis, Proctitis, Post-op prophylaxis,ileal Crohn’s, maintenance of remission, Microbiome- Concomitant meds- Can FMT make some patients worse?

Great success story for recurrent CDI

Being studied for multiple other conditions – IBD, IBS, ObesityAutism, NASH/Met synd, reversal of multidrug resistance to abx

IBD is associated with dysbiosis–More complicated than C. difficile

Patients are eager for alternative therapies

FMT appears generally “pretty safe”– Infections and disease flares have been reported

Therapeutic Manipulation of gut microbiota holds promise & mayeventually prove beneficial for other conditions– We must not be overly enthusiastic and remember that this isexperimental and unproven therapy.

FMT

Lachnospiraceae family

Faecalibacterium prausnitzii

Akkermansia muciniphila

Probiotic ecosystems

Microbiome - Future

“All disease begins in the gut”Hippocrates 460 BC – 370BC

“Health is determined by the microbiota in ourgut”

Hippocrates

Gut Microbiome

Gut Microbiome

Thank You